Cytokines regulate the antigen-presenting characteristics of human circulating and tissue-resident intestinal ILCs

Nat Commun. 2020 Apr 27;11(1):2049. doi: 10.1038/s41467-020-15695-x.

Abstract

ILCs and T helper cells have been shown to exert bi-directional regulation in mice. However, how crosstalk between ILCs and CD4+ T cells influences immune function in humans is unknown. Here we show that human intestinal ILCs co-localize with T cells in healthy and colorectal cancer tissue and display elevated HLA-DR expression in tumor and tumor-adjacent areas. Although mostly lacking co-stimulatory molecules ex vivo, intestinal and peripheral blood (PB) ILCs acquire antigen-presenting characteristics triggered by inflammasome-associated cytokines IL-1β and IL-18. IL-1β drives the expression of HLA-DR and co-stimulatory molecules on PB ILCs in an NF-κB-dependent manner, priming them as efficient inducers of cytomegalovirus-specific memory CD4+ T-cell responses. This effect is strongly inhibited by the anti-inflammatory cytokine TGF-β. Our results suggest that circulating and tissue-resident ILCs have the intrinsic capacity to respond to the immediate cytokine milieu and regulate local CD4+ T-cell responses, with potential implications for anti-tumor immunity and inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Colonic Neoplasms / immunology
  • Cytokines / immunology*
  • Humans
  • Immunity, Innate*
  • Inflammasomes / immunology
  • Interleukin-18 / immunology
  • Interleukin-1beta / immunology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Leukocytes, Mononuclear / immunology
  • Lymphocytes / immunology*
  • Mice

Substances

  • Cytokines
  • IL18 protein, human
  • IL1B protein, human
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta